Melanin is both photosensitizer and photoprotector. Skin cancer rates
decrease with increasing constitutive pigmentation, yet the pigment ha
s been shown to be photoreactive and capable of producing damaging rea
ctive oxygen species. We utilized model systems of related cells or si
milar cell type that vary in constitutive and in induced pigment. Indu
ction of eumelanin in Cloudman S91 mouse melanoma cells leads to less
UV-induced killing and to less mutation induction at the ouabain locus
(Na+, K+-ATPase). Pigmented mouse melanocytes, melan-b (brown) and me
lan-a (black) were slightly less sensitive than melcan-c (albino) mela
nocytes to killing after UVC and UVA but were more sensitive to killin
g after UVB and UVB + UVA. Pigment had a small sensitizing effect on p
yrimidine dimer DNA damage in both the melanoma cells and the melanocy
tes. The lack of consistency in these results suggests that intracellu
lar pigment may disregulate the milieu interieur resulting in end effe
cts that are unrelated to the original genomic damage.